TY - JOUR
T1 - Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients
AU - Maagdenberg, Hedy
AU - Bierings, Marc B.
AU - van Ommen, C. Heleen
AU - van der Meer, Felix J. M.
AU - Appel, Inge M.
AU - Tamminga, Rienk Y. J.
AU - Cessie, Saskia Le
AU - Swen, Jesse J.
AU - van der Straaten, Tahar
AU - de Boer, Anthonius
AU - Maitland-van der Zee, Anke H.
PY - 2018
Y1 - 2018
N2 - Aim: To study the effects of clinical and genetic factors on the phenprocoumon dose requirement in pediatric patients and to develop a dosing algorithm. Methods: Pediatric patients who used phenprocoumon were invited to participate in a retrospective follow-up study. Clinical information and genotypes of genetic variations in CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected and tested with linear regression for association with phenprocoumon dose requirement. Results: Of the 41 patients included in the analysis, age, VKORC1, CYP2C9∗2/∗3 and CYP3A4∗1B were statistically significantly associated with dose requirement, and together explained 80.4% of the variability in phenprocoumon dose requirement. Conclusion: Our study reveals that age and genetic variations explain a significant part of the variability in phenprocoumon dose requirement in pediatric patients.
AB - Aim: To study the effects of clinical and genetic factors on the phenprocoumon dose requirement in pediatric patients and to develop a dosing algorithm. Methods: Pediatric patients who used phenprocoumon were invited to participate in a retrospective follow-up study. Clinical information and genotypes of genetic variations in CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected and tested with linear regression for association with phenprocoumon dose requirement. Results: Of the 41 patients included in the analysis, age, VKORC1, CYP2C9∗2/∗3 and CYP3A4∗1B were statistically significantly associated with dose requirement, and together explained 80.4% of the variability in phenprocoumon dose requirement. Conclusion: Our study reveals that age and genetic variations explain a significant part of the variability in phenprocoumon dose requirement in pediatric patients.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054435251&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30207196
U2 - https://doi.org/10.2217/pgs-2018-0095
DO - https://doi.org/10.2217/pgs-2018-0095
M3 - Article
C2 - 30207196
SN - 1462-2416
VL - 19
SP - 1195
EP - 1202
JO - Pharmacogenomics
JF - Pharmacogenomics
IS - 15
ER -